Acute rejection remains a common cause of death, in the first year after heart transplantation. The essential histological features during the evolution of acute cardiac rejection comprises perivascular and interstitial mononuclear cell infiltrations, with myocyte damage. The intensity, immaturity and extension of mononuclear infiltrate, such as the severity of myocyte lesion define the grading of a rejection episode and the mode of immunosuppressive therapy. Arterio-occlusive disease, the main cause of death after the first year following transplantation, is characterized by concentric obliteration of coronary arteries.